Reaktion #1932410

Reaktionsgleichung

4′-methyl-5-((6-methylpyridin-3-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid

(3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate

N,N-diisopropylethylamine

trifluoroacetic acid

→

product

4′-Methyl-N-((6-methylpyridin-3-yl)methyl)-5-((3aR,6aS)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)biphenyl-3-carboxamide

Lösungsmittel

methylene chloride

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was purified by preparative HPLC
2. 2
   Sonstigeto yield Boc protected product as a white solid, which
3. 3
   workup.STIRRINGThe reaction mixture was stirred at rt overnight
4. 4
   SonstigeThe volatiles were removed in vacuo
5. 5
   Sonstigethe residue was purified by preparative HPLC (100×21.2 mm C18 column, 20-60% MeCN/water[10 mM Et2NH])

Vorschrift

To a solution of 4′-methyl-5-((6-methylpyridin-3-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid (25 mg, 0.069 mmol) in N,N-dimethylformamide (1 mL) were added (3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (30 mg, 0.14 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (60 mg, 0.16 mmol) and N,N-diisopropylethylamine (100 μL, 0.57 mmol). The reaction mixture was stirred for 16 hours at 25° C. The reaction mixture was purified by preparative HPLC to yield Boc protected product as a white solid, which was dissolved in methylene chloride (3.0 mL) and trifluoroacetic acid (0.20 mL, 2.6 mmol) was added. The reaction mixture was stirred at rt overnight. The volatiles were removed in vacuo and the residue was purified by preparative HPLC (100×21.2 mm C18 column, 20-60% MeCN/water[10 mM Et2NH]) to afford the product as a white foam.

Quelle